1. Field of the Invention
The present invention relates to a method for producing L-cysteine and related substances. Specifically, the present invention relates to a bacterium suitable for the production of L-cysteine and related substances and a method for producing L-cysteine and related substances utilizing the bacterium. L-cysteine and L-cysteine-related substances are utilized in the fields of drugs, cosmetics, and foods.
2. Brief Description of the Related Art
L-cysteine can be obtained by extraction from keratin-containing substances such as hair, horns and feathers, or by the conversion of the precursor DL-2-aminothiazoline-4-carboxylic acid using a microbial enzyme. L-cysteine has also been produced on a large scale by using an immobilized enzyme method and a novel enzyme. Furthermore, production of L-cysteine by fermentation utilizing a microorganism has also been attempted.
Microorganisms, which are able to produce L-cysteine, are also known. For example, a coryneform bacterium with increased intracellular serine acetyltransferase activity produces cysteine (Japanese Patent Laid-open (Kokai) No. 2002-233384). The ability to produce L-cysteine can also be increased by incorporating serine acetyltransferase which has been mutated to attenuate feedback inhibition by L-cysteine (Japanese Patent Laid-open No. 11-155571; U.S. Patent Published Application No. 20050112731; U.S. Pat. No. 6,218,168).
Furthermore, the ability to produce L-cysteine in a microorganism can be enhanced by suppressing the L-cysteine decomposition system. Examples of such microorganisms include coryneform bacteria or Escherichia bacteria in which the activity of cystathionine-β-lyase (Japanese Patent Laid-open No. 11-155571), tryptophanase (Japanese Patent Laid-open No. 2003-169668), or O-acetylserine sulfhydrylase B (Japanese Patent Laid-open No. 2005-245311) is attenuated or deleted.
Furthermore, the ydeD gene which encodes the YdeD protein participates in excretion of the metabolic products of the cysteine pathway (Dabler et al., Mol. Microbiol., 36, 1101-1112 (2000)). Also, techniques are known for enhancing L-cysteine-producing ability by increasing expression of the mar-locus, emr-locus, acr-locus, cmr-locus, mex-gene, bmr-gene or qacA-gene. These loci and/or genes encode proteins which cause secretion of toxic substances from cells (U.S. Pat. No. 5,972,663). The emrAB, emrKY, yojIH, acrEF, bcr, and cusA genes are further examples (Japanese Patent Laid-open No. 2005-287333).
An Escherichia coli has been reported which produces L-cysteine, and which has increased activity of the positive transcriptional control factor of the cysteine regulon encoded by the cysB gene (International Patent Publication WO01/27307).
Although the tolC gene (BioCyc Home Page, Summary of Escherichia coli, Strain K-12, version 11.6, E. coli K-12 Gene: tolC [searched on Feb. 11, 2008], Internet URL: biocyc.org/ECOLI/NEW-IMAGE?type=GENE&object=EG11009) is known as a gene coding for a porin (outer membrane channel), its relation to L-cysteine production is not known.